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Abstracts (complete list) - Wissenschaft Online

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Mario Zaiss, Jochen Zwerina, Karin Polzer, Eva Gückel, Alla Skapenko, Hendrick<br />

Schulze-Koops, Nikki Horwood, Andrew Cope, Georg Schett<br />

Regulatory T cells suppress osteoclast formation- a new link<br />

between the immune system and bone<br />

Objective.<br />

To investigate whether regulatory T cells can suppress osteoclast differentiation<br />

and to define a new potential link between the immune system and the skeleton.<br />

Methods.<br />

Regulatory CD4+CD25+foxp3+ T cells were isolated and purified from the spleen and<br />

co-cultured with CD11b+ osteoclast precursor cells isolated from the bone marrow.<br />

Osteoclastogenesis and bone erosion was assessed by TRAP staining and pit resorption<br />

assay, respectively. In addition, trans-well experiments and cytokine blocking<br />

experiments were performed to define the mechanisms of interaction between<br />

regulatory T cells and osteoclasts.<br />

Results.<br />

CD4+CD25+foxp3+ T cells dose dependently inhibited MCSF- and RANKL dependent<br />

osteoclast formation in contrast to CD4+CD25- T cells. Also pit formation was inhibited<br />

by up to 80%. The blockade of osteoclast formation was not based on an alteration of<br />

RANKL/OPG balance but essentially dependent on direct cell-cell contact via CTLA-4.<br />

Regulatory T cell-mediated expression of TGF-β, IL-4 and IL-10 contributed to the<br />

inhibitory effect on osteoclastogenesis, but was not essential.<br />

Conclusion.<br />

These data show that CD4+CD25+foxp3+ regulatory T cells suppress osteoclast<br />

formation. These data provide a new link between the immune system and bone and<br />

extend our knowledge on the regulation of bone homeostasis by the immune system.

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